Identification of aberrant gene expression during breast ductal carcinoma in situ progression to invasive ductal carcinoma

Journal of International Medical Research, Ahead of Print.


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Enhanced adsorption for Pb(II) and Cd(II) of magnetic rice husk biochar by KMnO 4 modification

Abstract

Novel KMnO₄-treated magnetic biochar (FMBC) was successfully synthesized by addition of Fe(NO₃)₃ during carbonization and KMnO₄ treatment following for Pb(II) and Cd(II) adsorption. SEM-EDS, XPS, and ICP-AES were used to evaluate the FMBC and magnetic biochar (FBC) on surface morphology, surface chemistry characteristics, surface functional groups, and Pb(II) and Cd(II) adsorption behavior. Results showed that the Langmuir maximum adsorption quantity of FMBC reached 148 mg/g for Pb(II) and 79 mg/g for Cd(II), nearly 7 times of that of FBC. The enhancement of FMBC for heavy metal adsorption was due to the successful load of manganese oxides and the increased oxygen functional groups consistent with XPS and FTIR results. The adsorption capacities of FMBC were maintained over 95% when the pH value was higher than 2.5 and 3.5 for Pb(II) and Cd(II), respectively. The adsorption performances of both heavy metals by FMBC were hardly influenced by ionic strength and humid acid. The adsorption capacities of FMBC could maintain over 50% and 87% after four cycles for Pb(II) and Cd(II), respectively. The saturation magnetization of FMBC was about 11.5 emu/g, which did not change after adsorption. This work proposed a new method to fabricate a magnetic biochar with high adsorption capacities of heavy metals Pb(II) and Cd(II).

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Sediment phosphorus release in response to flood event across different land covers in a restored wetland

Abstract

The phosphorus (P) fraction and its release characteristics from sediment in response to flood events across different land covers (i.e., reclaimed land with dominant vegetation of Phragmites australis and/or Typha orientalis, grassland with dominant vegetation of annual and perennial forbs, and bare land) in the lakeshore of Chaohu Lake were investigated. The results indicated that the re-flooding of a restored wetland led to P release. IP (inorganic P) was the major P fraction in the soils pre-flood and post-flood. For all the soil samples, the rank order of P fractions was Ca-P (P associated with calcium) > OP (organic P) > Fe/Al-P (P bound to Al, Fe, and Mn oxides and hydroxides). During flooding, Fe/Al-P contributed the most as the P release source in the soils and to the P sources for the overlying water. In reclaimed land, Fe/Al-P release correlated significantly with soil pH. In grassland, Fe/Al-P release correlated significantly with soil pH and Al content. In bare land, Fe/Al-P release correlated significantly with Al and clay content. The max TP release rates were also significantly influenced by land cover, and the values in bare land, grassland, and reclaimed land were 9.91 mg P m⁻² day⁻¹, 8.10 mg P m⁻² day⁻¹, and 5.05 mg P m⁻² day⁻¹, respectively. The results showed that the P release processes might be regulated by different factors across different land covers, and that the re-introduction of vegetation during wetland restoration must be taken into account prior to flood events to avoid an undesirable degradation of water quality.

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Evaluating giant panda as a surrogate species for conservation co-occurring species in the Baishuijiang National Nature Reserve

Abstract

The establishment of nature reserves is a key approach for biodiversity conservation worldwide. However, the effectiveness of nature reserves established by protecting the habitat needs of surrogate species is questioned. In this study, the Baishuijiang National Nature Reserve (Baishuijiang NNR), located in the Minshan Mountains, China, which is established mainly for the conservation of giant panda (a surrogate for the conservation of other endangered species) was selected. We quantitatively evaluated the conservation effectiveness of the reserve for giant panda and co-occurring species (here, seven protected species) using a maximum entropy model (Maxent), and analyzed spatial congruence between giant panda and other seven species. Results shown that the habitat of giant panda generally included the habitat of other seven protected species, suggesting that conservation of giant panda habitat also allows the conservation for the habitat of almost co-occurring species. Hence, the natural reserve established for giant panda as a surrogate species has a relatively high effectiveness. A high proportion of the suitable habitat for six species is inside the core zone, but a high proportion of the suitable habitat for two species is located in the experimental and buffer zones. Thus, the two species are affected by human activities. To improve the conservation effectiveness of the nature reserve, the management zones need to be amended. The result of the study will be beneficial for future conservation and management of the reserve. This study provides an effective method for evaluating the conservation effectiveness of nature reserves in other area of the worldwide.

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Impact of dietary nano-zinc oxide on immune response and antioxidant defense of broiler chickens

Abstract

This study aimed to elucidate the response of broiler chickens to the dietary nano-zinc supplementation in terms of immune response and antioxidant activity. Ninety-one-day-old chicks (Ross 308) were randomly assigned to one of three dietary treatments in three replicates, in a feeding trial that lasted for 5 weeks. Birds were fed a basal diet supplemented with inorganic zinc oxide at 40 mg/kg diet (control), zinc oxide nanoparticles (ZnONPs) at 40 mg/kg diet (ZN1), or ZnONPs at 80 mg/kg diet (ZN2). Birds were injected with DNP-KLH at the 7th and 21st days from the beginning of the experiment, and blood samples were collected on days 7, 14, 21, 28, and 35 to determine the levels of immunoglobulin Y (IgY) and malondialdehyde as well as the antioxidant enzyme activities. Cellular immunity was assayed by estimation of phagocytic percentage and index of peripheral monocytes of blood and estimation of the T lymphocyte activity using a lymphocyte transformation test. The results showed that feeding broiler chickens a diet supplemented with ZnONPs increased (p < 0.05) the activity of superoxide dismutase and catalase and decreased the concentration of malondialdehyde compared to the control diet, without significant differences between NZ1 and NZ2 diets. Moreover, the chicks fed diets supplemented with ZnONPs showed a significant increase (p < 0.05) in serum IgY, total lymphocyte count, and macrophages compared to the control. A higher significant response for antibodies IgY concentration was observed in birds fed the NZ2 vs NZ1 diet. Also, there was a significant increase in phagocytic activity and phagocytic index in ZnONP-fed groups with a higher significance in the group fed NZ1 than with NZ2 diet as compared with the control. In conclusion, ZnONP application up to 80 mg/kg in the diet is safe for broiler chickens and could improve their antioxidant defense and cellular immunity.

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The Possibilities of Using Chromium Salts as an Agent Supporting Treatment of Polycystic Ovary Syndrome

Abstract

The polycystic ovary syndrome (PCOS) is the most frequent endocrinopathy in women in reproductive age with the so far undetermined causes of development. In the etiopathogenesis of PCOS, the role of insulin resistance is emphasised, which was an indication for the attempts at using chromium III salts (Cr) in augmenting pharmacotherapy applied in patients. The analysis of the usefulness and efficacy of this approach was the direct goal of this thesis. Animal tests confirmed the efficacy of chromium in maintaining the appropriate level of glycaemia and insulinaemia, normalisation of plasma concentrations of microelements and also a correlation between the Cr level, insulin and dehydroepiandrosterone (DHEA) was found. A decrease in the expression of 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase was identified in adipose tissue. Clinical studies, although sparse, show that the supplementation with chromium can improve BMI and the parameters evaluating the control of glycaemia and increase the chances for ovulation and regular menstruation. However, the small number and a variability in study protocols makes comparing them very difficult. A completely new subject that has not been yet studied is the possibility of using chromium in levelling mood disorders in patients with PCOS. Currently, there are still no sufficient proofs for introducing chromium as a standard in treating and preventing insulin resistance in patients with PCOS. However, this direction remains open, and treating insulin resistance is an important challenge in clinical practice.

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Nanoanalytics: analytical methods for characterization of nano- and micro-objects

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Technologies for deodorization of malodorous gases

Abstract

There is an increasing number of citizens' complaints about odor nuisance due to production or service activity. High social awareness imposes pressure on entrepreneurs and service providers forcing them to undertake effective steps aimed at minimization of the effects of their activity, also with respect to emission of malodorous substances. The article presents information about various technologies used for gas deodorization. Known solutions can be included into two groups: technologies offering prevention of emissions, and methodological solutions that enable removal of malodorous substances from the stream of emitted gases. It is obvious that the selection of deodorization technologies is conditioned by many factors, and it should be preceded by an in-depth analysis of possibilities and limitations offered by various solutions. The aim of the article is presentation of the available gas deodorization technologies as to facilitate the potential investors with selection of the method of malodorous gases emission limitation, suitable for particular conditions.

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Huge rhinophyma in a complicated patient successfully treated with C02 laser

Abstract

Rhinophyma is a bothersome and disfiguring condition of the nose that is often cause of cosmetic embarrassment and social reclusion.

Nowadays the therapeutic possibilities are highly variable and have to be personalized case by case. These possibilities include pharmacological therapy, laser surgery, mechanical dermabrasion and surgical excision. For patients with cardiovascular comorbidies and anticoagulant therapy, the therapeutic choice is limited. We present a case of a giant rhinophyma in a patient with several comorbidities that we successfully treated with CO2 laser.

This article is protected by copyright. All rights reserved.

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Superhydrophilic Phytic Acid‐doped Conductive Hydrogels as Metal‐free and Binder‐free Electrocatalysts for Efficient Water Oxidation

Recently, metal‐free heteroatoms doped‐carbon nanomaterials have emerged as promising electrocatalysts for oxygen evolution reaction (OER), but the synthesis of them suffers from tedious process involving energy‐wasting calcination. The molecular electrocatalysts offer attractive substitutes for OER; especially, natural organic molecules, i.e. phytic acid (PA), have advantages of easy production, low‐cost and environment‐friendly. Here, we selected PA as platform molecules to investigate the activity of carbons on organic molecules by means of DFT calculations and experiments. The results indicated that the positively charged carbons on PA were very active for OER. And then, the PA molecules were fixed into a porous and conductive hydrogel with a superhydrophilic surface, which was directly exploited as a metal‐free electrocatalyst for OER, revealing a small overpotential of 340 mV at 10 mA cm‐2, a Tafel slope of 54.9 mV dec‐1, and outstanding stability of 20 h, outperforming most metal‐free electrocatalysts. Besides the active sites on PA, the high OER activity was also related to the porous and conductive networks on the hydrogel, which allowed fast charge and mass transport during OER. Therefore, this work provided a metal‐free organic molecule‐based electrocatalyst to replace carbon nanomaterials for efficient OER.

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A soil bacterium can shape belowground interactions between maize, herbivores and entomopathogenic nematodes

Abstract

Background and aim

Entomopathogenic nematodes (EPN) use odor cues to locate and infect their insect hosts in the soil, making them an important tool in sustainable management of agricultural insect pests. However, very little information is available on the role of soil bacteria in mediating belowground interactions between plants, herbivores and the EPN. In this study, a maize-herbivore-entomopathogenic nematode complex was used to investigate the effect of plant root colonization by a soil bacterium on belowground tritrophic interactions.

Methods

The impact of maize root colonization by Bacillus pumilus strain INR-7 on the preference of the EPN, Heterorhabditis bacteriophora was tested in four arm olfactometer bioassays in the presence or absence of the root herbivore Diabrotica virgifera LeConte (Coleoptera: Chrysomelidae). Plant volatiles were collected for profile characterization. Further preference assays were performed using plant volatile extracts and synthetic volatiles.

Results

In the absence of the root herbivore, the nematodes were attracted to maize roots whose seeds were coated with dead and living bacteria. In the presence of the herbivore, the nematodes selectively oriented towards infested plants whose seeds were treated with B. pumilus strain INR-7 than dead bacteria treated, untreated plants or sunshine sand mix. In contrast, plant volatile extracts or pure compounds did not reproduce the observed behavior.

Conclusions

The study showed that bacterial coating of maize seeds with the tested strain may play an important role in shaping belowground tritrophic interactions through mechanisms that would require further investigations. The potential of B. pumilus strain INR-7 integration in maize rootworm management program is discussed.

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Ancient human genome-wide data from a 3000-year interval in the Caucasus corresponds with eco-geographic regions

Ancient human genome-wide data from a 3000-year interval in the Caucasus corresponds with eco-geographic regions

Ancient human genome-wide data from a 3000-year interval in the Caucasus corresponds with eco-geographic regions, Published online: 04 February 2019; doi:10.1038/s41467-018-08220-8

The Caucasus mountain range has impacted on the culture and genetics of the wider region. Here, the authors generate genome-wide SNP data for 45 Eneolithic and Bronze Age individuals across the Caucasus, and find distinct genetic clusters between mountain and steppe zones as well as occasional gene-flow.

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Ancient human genome-wide data from a 3000-year interval in the Caucasus corresponds with eco-geographic regions

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Attenuation of hyperhomocysteinemia induced vascular dementia by sodium orthovanadate perhaps via PTP1B: pertinent downstream outcomes

Publication date: Available online 2 February 2019

Source: Behavioural Brain Research

Author(s): Sandeep Kumar, Sergey Ivanov, Alexey Lagunin, Rajesh Kumar Goel

Abstract

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's disease, but drug regulatory authorities have not approved any effective medication for this indication. Researchers are keenly aware of the need to uncover precise and druggable targets for VaD. However, finding such a target is an experimentally impractical and challenging task, owing to the highly complex interplay between cognitive and functional abilities of the brain with a diversity of vascular diseases that usually results from various underlying risk factors. Network pharmacology, may, therefore be an alternative and rational choice because a network of disease targets let researchers select the best target from a disease module. According to this approach, inhibition of protein tyrosine phosphatase 1B (PTP1B) may trigger downstream effects of VaD relevance, but specific inhibitors of this enzyme are currently not in medical use. To assess whether PTP1B mediated actions are possible and are relevant to VaD or not, the impact of sodium orthovanadate on homocysteine-induced endothelial dysfunction, oxidative stress, cholinergic dysfunction learning and memory impairments investigated. The visual, spatial, emotional and fear-motivated learning, and memory impairment assessed by object recognition, water maze, step-through and elevated plus maze task, respectively. These impairments significantly attenuated by sodium orthovanadate, therefore, downstream effects seems to be relevant, and the role of PTP1B is suspected. However, sodium orthovanadate is a non-specific inhibitor of PTP1B; therefore, further in-vivo validation warranted, and it is possible in future because specific PTP1B inhibitors are in development phase.

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Melanoma central nervous system metastases: An update to approaches, challenges, and opportunities

Summary

In February 2018, the Melanoma Research Foundation and the Moffitt Cancer Center hosted the Second Summit on Melanoma Central Nervous System (CNS) Metastases in Tampa, Florida. In this white paper we outline the current status of basic science, translational and clinical research into melanoma brain metastasis development and therapeutic management. We further outline the important challenges that remain for the field and the critical barriers that need to be overcome for continued progress to be made in this clinically difficult area.

This article is protected by copyright. All rights reserved.

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Pediatric Facial Trauma

Publication date: Available online 2 February 2019

Source: Clinics in Plastic Surgery

Author(s): Tom W. Andrew, Roshan Morbia, H. Peter Lorenz

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Expanding the Spectrum of Intraosseous Rhabdomyosarcoma: Correlation Between 2 Distinct Gene Fusions and Phenotype

Primary intraosseous rhabdomyosarcomas (RMSs) are extremely rare. Recently 2 studies reported 4 cases of primary intraosseous RMS with EWSR1/FUS-TFCP2 gene fusions, associated with somewhat conflicting histologic features, ranging from spindle to epithelioid. In this study we sought to further investigate the pathologic and molecular abnormalities of a larger group of intraosseous RMSs by a combined approach using targeted RNA sequencing analysis and fluorescence in situ hybridization (FISH). We identified 7 cases, 3 males and 4 females, all in young adults, age range 20 to 39 years (median, 27 y). Three cases involved the pelvis, 2 involved the femur and 1 each involved the maxilla and the skull. Molecular studies identified recurrent gene fusions in all 7 cases tested, including: a novel MEIS1-NCOA2 fusion in 2 cases, EWSR1-TFCP2 in 3 cases, and FUS-TFCP2 gene fusions in 1 case. One case showed a FUS gene rearrangement, without a TFCP2 gene abnormality by FISH. The MEIS1-NCOA2–positive cases were characterized by a more primitive and fascicular spindle cell appearance, while the EWSR1/FUS rearranged tumors had a hybrid spindle and epithelioid phenotype, with more abundant eosinophilic cytoplasm and mild nuclear pleomorphism. Immunohistochemically, all tumors were positive for desmin and myogenin (focal). In addition, 4 tumors with TFCP2-associated gene fusions also coexpressed ALK and cytokeratin. In conclusion, our results suggest a high incidence of gene fusions in primary RMSs of bone, with 2 molecular subsets emerging, defined by either MEIS1-NCOA2 or EWSR1/FUS-TFCP2 fusions, showing distinct morphology and immunophenotype. Additional studies with larger numbers of cases and longer follow-up data are required to definitively evaluate the biological behavior of these tumors and to establish their relationship to other spindle cell RMS genetic groups. Conflicts of Interest and Source of Funding: Supported by P50 CA 140146-01 (CRA), Cycle for Survival (CRA), Slifka Foundation (CRA), and St Baldrick Foundation (CRA). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Cristina R. Antonescu, MD, Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065 (e-mail: antonesc@mskcc.org). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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90Y-TheraSpheres: The New Look of Yttrium-90

Selective internal radiation therapy with 90Y-TheraSphere or 90Y-SIRSphere is used in the treatment of unresectable hepatic malignancies. To the best of our knowledge, this is the first 90Y-TheraSpheres series. BTG International Canada Inc. provided nonradiated microspheres from the Nordion manufacturer. The histologic processed microspheres were colorless, refractile, polarizable, 20 to 30 μm in diameter, and an occasional internal bulls'-eye seen with the condenser out and an internal cross seen with polarized light. Identical microspheres were identified in 15 hepatectomy specimens from four centers between February 2016 and March 2018. The patients were usually male (male=10, female=5) with a mean age of 59 years. All patients had a prior diagnosis of hepatocellular carcinoma (HCC) and documented 90Y-TheraSphere (mean duration from last deployment=32 wk). All surgical pathology specimens in these 15 patients were reviewed, but the microspheres were only identified in the hepatectomy specimens. During manuscript preparation, one case of 90Y-TheraSpheres gastritis was prospectively identified from a separate patient with a history of HCC and 90Y-TheraSpheres. In conclusion, recognition of 90Y-TheraSpheres is important so that one may consider the possibility of a nearby malignancy and or establish the cause of the background inflammatory or radiation-related injury. These structures can be easy to miss because the subtle morphology is distinct from previously reported 90Y-SIRSphere. Clues to the diagnosis include a history of HCC and background radiation change. We report the characteristic morphology as microspheres that overlap in size with 90Y-SIRSphere, but can be differentiated based on 90Y-TheraSpheres' colorless appearance with occasional internal bulls'-eyes with the condenser out and an internal cross with polarized light. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Christina A. Arnold, MD, Department of Pathology; The Ohio State University Wexner Medical Center; 410 W. 10th Avenue; Columbus, OH 43210-1228 (e-mail christina.arnold@OSUMC.edu). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Clinical Outcomes of HPV-associated and Unassociated Endocervical Adenocarcinomas Categorized by the International Endocervical Adenocarcinoma Criteria and Classification (IECC)

The International Endocervical Adenocarcinoma Criteria and Classification (IECC) categorizes endocervical adenocarcinomas (ECAs) on the basis of morphologic features linked to etiology (ie, human papilloma virus [HPV] infection), resulting in separation of ECAs into HPV-associated (HPVA) and unassociated or non-HPVA (NHPVA) types. NHPVAs are reported to be large and present at high stage in older individuals. Our aim was to examine the clinical outcomes in these tumor types. Full slide sets of 205 ECAs were collected from 7 institutions worldwide and classified on the basis of IECC criteria and the presence or absence of HPV. Clinical and morphologic parameters were correlated with follow-up data. Statistical analysis of overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were conducted using the Kaplan-Meier survival analysis and compared using the log-rank test for univariate analysis. Multivariate survival analysis was conducted, and the survival endpoints considered were OS, DFS, and PFS. Statistically significant survival differences (OS, DFS, and PFS) were found when comparing the following categories: HPVA>NHPVA (ie, survival was superior in the setting of HPVAs), including patients treated with surgery followed by adjuvant therapy; usual-type HPVA>mucinous HPVA; FIGO grade 3 HPVA>NHPVA; HPVA>NHPVA, both with lymphovascular invasion; and HPVA>NHPVA in patients with pelvic recurrences. Although there were trends favoring HPVA outcomes over those of NHPVA, these differences were not statistically significant in the following categories: mucinous HPVA versus NHPVA; HPVA versus NHPVA, both with lymph node metastases at presentation; and HPVA versus NHPVA in patients with distant metastasis. Survival for both HPVA and NHPVA was similar when surgery without adjuvant therapy was used. FIGO grading did not have prognostic significance in HPVAs. Multivariable analysis of HPVAs indicated nearly significant statistical associations between stage and both OS and DFS (P=0.07 and 0.06, respectively), and between Silva invasion pattern and OS (P=0.09). Multivariate analysis of NHPVAs indicated a statistically significant association between OS and age (P=0.03), stage (P=0.02) and tumor size (P=0.002), and between DFS and stage (P=0.004) and tumor size (P=0.004). Multivariate analysis of HPVAs and NHPVAs together revealed nearly significant associations between OS and HPV status and stage (both [P=0.06]). For DFS, stage was a significant variable (P=0.04), whereas HPV status and tumor size were nearly significant (P=0.06 and 0.07, respectively). Clinical outcome studies support the idea that the IECC classification not only separates ECAs on the basis of HPV status (usually assessed on H&E slides), but also has important clinical relevance. Conflicts of Interest and Sources of Funding: Supported in part through the NIH/NCI Support Grant P30 CA008748 (R.A.S., K.J.P., N.R.A.-R.). Correspondence: Robert A. Soslow, MD, Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (e-mail: soslowr@mskcc.org). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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"Shelter technique" in the treatment of ossification of posterior longitudinal ligament involving C2 segment.

"Shelter technique" in the treatment of ossification of posterior longitudinal ligament involving C2 segment.

World Neurosurg. 2019 Jan 30;:

Authors: Sun J, Sun K, Wang S, Yang H, Wang Y, Xu X, Shi J

Abstract
PURPOSE: Anterior or posterior decompression has been widely used to treat patients with ossification of posterior longitudinal ligament (OPLL). However, when OPLL extends to C2 level, the complex anatomic structures around C2 vertebral body and postoperative destabilization or kyphosis would make it difficult to perform anterior or posterior surgery. This study proposed a novel technique named "shelter technique" to deal with C2-OPLL.
METHODS: Sixteen patients with cervical OPLL involving C2 segment were included. The OPLL below C2 was dealt with anterior controllable antedisplacement and fusion (ACAF), including discectomy of involved levels, resection of the anterior vertebral bodies, installation of the intervertebral cages and anterior cervical plate, isolation of vertebrae-OPLL complex (VOC), and the final hoisting of the VOC. when dealing with C2-OPLL, the posterior portion of C2 vertebral body was resected to create the "shelter" based on the thickness of C2-OPLL, which could provide space for further antedisplacement of ossified mass behind C2 vertebrae. Finally, OPLL behind C2 was moved forward together with the antedisplacement of VOC below C2.
RESULTS: Postoperative MRI and CT showed sufficient decompression of the spinal cord including C2 segment, and the "shelter" provided enough space for the antedisplacement of ossified mass behind C2 segment. At the final follow-up of one year, neurological function of all patients recovered significantly.
CONCLUSION: The shelter technique can be relatively effective and safe for patients with OPLL involving C2 segment. However, further studies with more cases and longer follow-up will be required to reveal the surgical value of the technique.

PMID: 30710725 [PubMed - as supplied by publisher]

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Long term clinical outcome and reoperation rate for microsurgical bilateral decompression via unilateral approach of lumbar spinal stenosis.

Long term clinical outcome and reoperation rate for microsurgical bilateral decompression via unilateral approach of lumbar spinal stenosis.

World Neurosurg. 2019 Jan 30;:

Authors: Yüce İ, Kahyaoğlu O, Çavuşoğlu HA, Çavuşoğlu H, Aydın Y

Abstract
BACKGROUND: Lumbar stenosis is a common degenerative spinal disease of the lumbar spine. The aim of our observational prospective study is to evaluate the long-term outcome and reoperation rate (RR) after microsurgical bilateral decompression via unilateral approach (BDUA) for lumbar spinal stenosis (LSS).
METHODS: Nine hundred and eighteen patients were treated for single or multilevel LSS by BDUA between January 2002 and January 2016. 180 patients of the 918 underwent microdiscectomy with decompression. They were then followed up postoperatively, at 6 and 12 months with radiological investigations, Oswestry Disability Index (ODI) and 36-item short-form health survey (SF-36) tests.
RESULT: Four hundred and ninety-two patients were females (53,6%), four hundred and twenty six were males (46,4) whose mean age was 63,83±10,16 (range: 43-79 years). Duration of symptoms ranged from 4 to 49 months. Average follow-up time was 98 months (range 25-168 months) and the RR was 2,5%. The ODI scores decreased significantly (30.65± 7.82, to 11.32 ± 2.50 at six months and 11.30 ± 2.49 at first year) and the SF-36 parameter scores demonstrated a significant improvement in the early and late follow-up results.
CONCLUSIONS: BDUA for LSS allowed a sufficient and safe decompression of the neural structures, resulted in a highly significant reduction of the symptoms and disability, acceptable RR, and improved health-related quality of life.

PMID: 30710724 [PubMed - as supplied by publisher]

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EGFR mutation status confers survival benefit in non-small cell lung cancer patients undergoing surgical resection of brain metastases: a retrospective cohort study.

EGFR mutation status confers survival benefit in non-small cell lung cancer patients undergoing surgical resection of brain metastases: a retrospective cohort study.

World Neurosurg. 2019 Jan 30;:

Authors: Huang Y, Chow KKH, Aredo JV, Padda SK, Han SS, Kakusa BW, Gephart MH

Abstract
BACKGROUND: Few prognostic markers are available for NSCLC patients undergoing neurosurgical resection of symptomatic brain metastases.
OBJECTIVE: We investigated whether tumor mutation status (EGFR, KRAS, ALK, ROS1, BRAF) and treatment history were associated with survival after neurosurgery.
METHODS: We reviewed the electronic health records of 104 NSCLC patients with genomic profiling who underwent neurosurgical resection for symptomatic brain metastases at an academic institution between January 2000 and January 2018. We used multivariate Cox proportional hazards regression models to evaluate the association between overall survival (OS) after neurosurgery and clinico-pathological factors including mutation status.
RESULTS: Mean age of patients in this study was 61 (±12) years, and 44% were men. The median OS after neurosurgery was 24 months (95% confidence interval: 18-34). Our multivariate analysis showed that the presence of an EGFR mutation in the tumor was significantly associated with improved OS (hazard ratio [HR] 0.214 p = 0.029), independent of tyrosine kinase inhibitor (TKI) use. Presence of KRAS, ALK, ROS1 and BRAF alterations were not associated with survival (all p > 0.05). Conversely, older age (HR: 1.039; p=0.029), a history of multiple brain irradiation procedures (HR 9.197; p < 0.001) and presence of extracranial metastasis (HR 2.556; p = 0.016) resulted in increased risk of mortality.
CONCLUSION: Patients requiring surgical resection of an EGFR mutated NSCLC brain metastasis had an associated improved survival compared to patients without this mutation, independent of TKI use. Decreased survival was associated with older age, multiple prior brain radiation therapies and extracranial metastasis.

PMID: 30710723 [PubMed - as supplied by publisher]

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Percutaneous Endoscopic Lumbar Discectomy for Axillar Herniation at L5-S1 via the Transforaminal Approach Versus the Interlaminar Approach: A Prospective Clinical Trial.

Percutaneous Endoscopic Lumbar Discectomy for Axillar Herniation at L5-S1 via the Transforaminal Approach Versus the Interlaminar Approach: A Prospective Clinical Trial.

World Neurosurg. 2019 Jan 30;:

Authors: Mo X, Shen J, Jiang W, Zhang X, Zhou N, Wang Y, Hao J

Abstract
OBJECTIVE: To evaluate the results of percutaneous endoscopic transforaminal discectomy (PETD) in comparison with percutaneous endoscopic interlaminar discectomy (PEID) for axillar herniation at L5-S1.
METHODS: From January 2017 to March 2018, 80 patients admitted with axillar herniation at L5-S1 were randomly recruited into two groups: 40 cases in the PETD group and 40 in the PEID group. Each group separately underwent PETD or PEID. Patient sex, age, body mass index (BMI), axillar herniation size, number of C-arm fluoroscopies, operation time, postoperative bed time, complications, and clinical effect were compared. Both groups were followed up using the Oswestry Disability Index (ODI), visual analogue scale (VAS) and MacNab criteria.
RESULTS: Except for one case in the PETD group that switched to the PEID group, the patients completed the study as expected. All patients were followed up. Preoperative demographics were not significantly different (P > 0.05) between the two groups. The mean number of C-arm fluoroscopies (12.44 ± 3.21) and the operation time (66.49 ± 16.29 minutes)of PETD group were significantly improved compared with the PEID group (number of fluoroscopies: 3.41 ± 0.81, P < 0.001; operation time: 53.56 ± 10.82 minutes, P < 0.001), but the postoperative bed rest time and complication rate were not (P > 0.05). The postoperative ODI and VAS scores were obviously improved in both groups when compared with preoperation (P < 0.001). There were no significant differences between the 2 groups in MacNab criteria or VAS and ODI scores at the same time point (P > 0.05).
CONCLUSIONS: For axillar herniation at L5-S1, PEID can ignore the anatomic obstruction with advantages including a shorter operation time and less intraoperative radiation exposure. PETD has a clinical effect similar to that of PEID, but the process of it is more dangerous and harder than PEID.

PMID: 30710722 [PubMed - as supplied by publisher]

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Percutaneous Doxycycline Foam Injections, A Novel Treatment Method for Vertebral Aneurysmal Bone Cysts.

Percutaneous Doxycycline Foam Injections, A Novel Treatment Method for Vertebral Aneurysmal Bone Cysts.

World Neurosurg. 2019 Jan 30;:

Authors: Lyons KW, Borsinger TM, Pearson AM

PMID: 30710721 [PubMed - as supplied by publisher]

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Progesterone is more effective than dexamethasone in prolonging overall survival and preserving neurologic functions in experimental animals with orthotopic glioblastoma allografts.

Progesterone is more effective than dexamethasone in prolonging overall survival and preserving neurologic functions in experimental animals with orthotopic glioblastoma allografts.

World Neurosurg. 2019 Jan 30;:

Authors: Cheng Y, Yeung WL, De Zhang P, Li N, Kiang MY, Leung KK

Abstract
OBJECTIVE: Dexamethasone (DEXA) is widely used in the management of peri-tumoral brain edema. DEXA, however, has many systemic side-effects, and may interact negatively with glioma therapy. Progesterone (PROG), on the other hand, is a well-tolerated and readily accessible anti-inflammatory and anti-edema agent with potent neuroprotective properties. We investigated if PROG can serve as a viable alternative to DEXA in the management of peri-tumoral brain edema.
METHODS: We used an orthotopic C6 glioblastoma model with male Sprague-Dawley (SD) rats. Tumor grafts were allowed to grow for 14 days prior to drug treatment with (i) DEXA 1mg/kg, (ii) PROG 10mg/kg or (iii) PROG 20 mg/kg for five consecutive days. Overall animal survival and neurologic functions were evaluated. Mechanistic studies on blood brain barrier (BBB) permeability and angiogenic responses were performed on the ex vivo tumor grafts.
RESULTS: We found that all drug treatments prolonged overall survival to different extents. PROG 10mg led to significantly longer survival, and better preservation of neurologic functions and body weight. BBB permeability was better preserved with PROG 10mg than DEXA possibly through the downregulation of MMP-9 and AQP-4 expressions; anti-angiogenic responses were also observed in the PROG group.
CONCLUSIONS: This proof-of-concept pilot study provides novel information on the use of PROG as a corticosteroids-sparing agent in brain tumor management. Further translational and clinical studies are warranted.

PMID: 30710720 [PubMed - as supplied by publisher]

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Systematic and Comprehensive Comparison of Incidence of Restenosis between Carotid Endarterectomy and Carotid Artery Stenting in the Patients with Atherosclerotic Carotid Stenosis.

Systematic and Comprehensive Comparison of Incidence of Restenosis between Carotid Endarterectomy and Carotid Artery Stenting in the Patients with Atherosclerotic Carotid Stenosis.

World Neurosurg. 2019 Jan 30;:

Authors: Xin WQ, Li MQ, Li K, Li QF, Zhao Y, Wang WH, Gao YK, Wang HY

Abstract
OBJECTIVE: The purpose of this study was to conduct a meta-analysis to systematically compare the incidence rates of in-stent restenosis after CAS and restenosis after CEA for patients with atherosclerotic carotid stenosis.
METHOD: This study retrieved potential academic articles comparing restenosis between Carotid Endarterectomy (CEA) and Carotid Artery Stenting (CAS) from the MEDLINE database, the PubMed database the EMBASE database, and the Cochrane Library from the period between the date of the first CEA, performed in January 1951, and July 20, 2018. The reference articles for the identified studies were carefully reviewed to ensure that all available documents were represented in the study.
RESULT: A total of 27 articles (15 RCTs, 12 non-RCTs) including 20,479 participants with atherosclerotic carotid stenosis were included in our meta-analysis. There was a significant difference in the cumulative incidence of restenosis >70% between endarterectomy and stenting [RD=-0.033, 95% CI (-0.054 - -0.013) P=0.002]. In terms of restenosis >70% outcomes, although CEA was relevant with a lower rate of restenosis than CAS within 0.5 years [OR=0.495, 95% CI (0.285-0.861) P=0.013] and 1 year [OR=0.626, 95% CI (0.483-0.811), P<0.001], no statistically significant differences were found at 1.5 years (P=0.210), 2 years (P=0.123), 4 years (P=0.124), 5 years (P=0.327) and 10 years (P=0.839). Similarly, in terms of restenosis >50% outcomes, a significant difference was shown in the rates of restenosis between the endarterectomy and stenting groups within 1 year [OR =0.317, 95% CI (0.228-0.441), P<0.001], but not at 1.5 years (P=0.301), 2 years (P=0.686) or 5 years (P=0.920). Simultaneously, no nominally significant effects were demonstrated with respect to the cumulative incidence of occlusion (P=0.195) and the cumulative incidence of restenosis for symptomatic patients (P=0.170) between endarterectomy and stenting.
CONCLUSIONS: Although CAS was preferred over restenosis regardless of restenosis >50% or 70% after revascularization within 1 year, no significant difference was observed with extension of the follow-up period to more than 1 year. Simultaneously, CAS was not associated with a higher cumulative incidence of occlusion and the cumulative incidence of restenosis for symptomatic patients.

PMID: 30710719 [PubMed - as supplied by publisher]

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A rare case of negative pressure hydrocephalus: a plausible explanation and the role of transmantle theory.

A rare case of negative pressure hydrocephalus: a plausible explanation and the role of transmantle theory.

World Neurosurg. 2019 Jan 30;:

Authors: Diaz-Romero Paz R, Altimira PA, Valverde GC, Martin CB

Abstract
BACKGROUND: Negative-pressure hydrocephalus is a rare condition with the development of symptomatic hydrocephalus despite subnormal intracranial pressure (ICP). The etiology remains unclear. Some authors proposed that the differential pressure between the ventricular space and the subarachnoid space (SAS) over cerebral convexity leads to the development of ventriculomegaly, namely as the transmantle pressure theory.
CASE DESCRIPTION: A 49-year-old with a left Sylvian fissure arachnoid cyst underwent several surgeries including cystoperitoneal shunts and fenestrations of the cyst. The patient developed a CSF fistula from the cranial wound complicated by bacterial meningitis. Consequently, the shunt was removed, and external cyst drainage was placed. After 9 days, the patient developed acute hydrocephalus requiring external ventricular drainage. Two days later, after overdrainage of the external cyst drain, the patient suffered neurological deterioration. The ICP measured by the EVD was -4 cm H2O and a CT demonstrated progression of the hydrocephalus. The ECD was shut off and the EVD level was adjusted to produce between 5 and 10 mL/hour of CSF under a subatmospheric pressure set at -5 cm H2O and gradually raised in increments of 1 cm every 3 days until a positive ICP occurred. Once clinical and radiographic stability was accomplished, a programmable ventriculoperitoneal shunt was inserted set to 30 mm H2O. A marked clinical and radiological improvement was observed in the follow-up.
CONCLUSIONS: This NePH case report supports the main role of the transmantle pressure theory. The subatmospheric EVD method and a low-pressure valve resulted in excellent clinical and radiographic outcomes.

PMID: 30710718 [PubMed - as supplied by publisher]

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Variation in guideline implementation and adherence regarding severe traumatic brain injury treatment: a CENTER-TBI survey study in Europe.

Variation in guideline implementation and adherence regarding severe traumatic brain injury treatment: a CENTER-TBI survey study in Europe.

World Neurosurg. 2019 Jan 30;:

Authors: Volovici V, Ercole A, Citerio G, Stocchetti N, Haitsma IK, Huijben JA, Dirven CMF, van der Jagt M, Steyerberg EW, Nelson D, Cnossen MC, Maas AIR, Polinder S, Menon DK, Lingsma HF, CENTER – TBI collaborators

Abstract
Guidelines may reduce practice variation and optimize patient care. We aimed to study differences in guideline use in the management of traumatic brain injury (TBI) patients and analyze reasons for guideline non-adherence. As part of a prospective, observational, multi-center European cohort study, participants from 68 centers in 20 countries were asked to complete 72-item questionnaires regarding their management of severe TBI. Six questions with multiple sub-questions focused on guideline use and implementation. Questionnaires were completed by 65 centers. Of these, 49 (75%) reported use of the Brain Trauma Foundation Guidelines for the medical management of TBI or related institutional protocols, 11 (17%) used no guidelines and 5 used other guidelines (8%). Of 54 centers reporting use of any guidelines, 41 (75%) relied on written guidelines. Four centers of the 54 (7%) reported no formal implementation efforts. Structural attention to the guidelines during daily clinical rounds was reported by 21 centers (38%). The most often reported reasons for non-adherence were 'every patient is unique' and the presence of extracranial injuries, both for centers that did and did not report the use of guidelines. There is substantial variability in the use and implementation of guidelines in neurotrauma centers in Europe. Further research is needed to strengthen the evidence underlying guidelines and to overcome implementation barriers.

PMID: 30710717 [PubMed - as supplied by publisher]

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Salvage Stereotactic Radiosurgery in Breast Cancer Patients With Multiple Brain Metastases.

Salvage Stereotactic Radiosurgery in Breast Cancer Patients With Multiple Brain Metastases.

World Neurosurg. 2019 Jan 30;:

Authors: Perez JL, Ozpinar A, Kano H, Phan B, Niranjan A, Lunsford LD

Abstract
BACKGROUND: The overall survival rates for breast cancer are increasing due to controlled brain disease and improved systemic treatments. This study examined neurological outcomes, tumor control, and survival data in breast cancer patients with multiple brain metastases, and who required salvage stereotactic radiosurgery (SRS) for recurrent breast cancer brain metastases.
METHODS: The study included 231 patients with a primary diagnosis of breast cancer who underwent SRS for greater than one brain metastases from May 1993 and July 2007. Survival analyses via univariate and multivariate Cox regression demonstrated interactions between survival and predictor values including KPS, RPA Class, number of brain metastases, whole brain radiotherapy (WBRT), immunotherapy, and chemotherapy.
RESULTS: Of the 231 patients, the survival rate was 53% at 1 year and 26% at 5 years from initial SRS. Controlled systemic disease, adjuvant chemotherapy, and RPA Class II were significant predictors of increased survival, while WBRT was a significant predictor of decreased survival. The median survival in patients who received WBRT after SRS was 11 months versus 23 months in those who did not. The local tumor control rate at initial follow-up was 95%. Of these, 40% of patients underwent additional brain SRS. Following salvage SRS, 8% of patients developed symptomatic adverse radiation events (ARE), however, the development of symptomatic ARE had no effect on patient survival.
CONCLUSIONS: This report indicated that both initial and salvage SRS procedures in breast cancer patients with multiple brain metastases is effective for local control of intracranial disease, while minimizing adverse radiation effects.

PMID: 30710716 [PubMed - as supplied by publisher]

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Neurosurgery Rounds: Questions and Answers: Second Edition.

Neurosurgery Rounds: Questions and Answers: Second Edition.

World Neurosurg. 2019 Jan 30;:

Authors: Gupta M, Ben-Haim S

PMID: 30710715 [PubMed - as supplied by publisher]

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A Case of Primary Aldosteronism Due to A Primary Adrenal Adenoma Diagnosed by Segmental Adrenal Venous Sampling (S-AVS) Using a Modified Catheter System and Lateral Cine Angiography.

A Case of Primary Aldosteronism Due to A Primary Adrenal Adenoma Diagnosed by Segmental Adrenal Venous Sampling (S-AVS) Using a Modified Catheter System and Lateral Cine Angiography.

Am J Case Rep. 2019 Feb 02;20:139-145

Authors: Okamura K, Okuda T, Fukuda Y, Takamiya Y, Shirai K, Miyajima S, Ishii T, Urata H

Abstract
BACKGROUND Before partial adrenalectomy for primary aldosteronism due to a primary adrenal adenoma, the aldosterone-producing tumor can be localized by segmental adrenal vein sampling (S-AVS). Cardiologists, who regularly perform percutaneous coronary intervention (PCI), or coronary angioplasty with stent, may not be familiar with the technique of S-AVS. A case of the use of S-AVS is reported in a patient who presented with primary aldosteronism and a right adrenal adenoma. CASE REPORT A 44-year-old man with a history of hypertension presented with a man in the posterior part of the right adrenal gland. He had hypokalemia, and a high plasma aldosterone concentration/plasma renin activity ratio. A captopril stress test confirmed the diagnosis of primary aldosteronism. Pre-operative S-AVS was performed using a microwire and microcatheter, which were advanced into the segmental adrenal vein using a 6.5 French guiding catheter and a Y-shaped connector, under biplane cine angiography guidance. S-AVS showed a high plasma aldosterone concentration in the right superior tributary adrenal vein draining the adrenal mass. Right partial adrenalectomy was performed. Postoperatively, the patient's blood pressure and plasma aldosterone levels normalized. CONCLUSIONS S-AVS can be performed relatively easily before partial adrenalectomy using a catheter system with biplane cine angiography, which is a technique that is familiar to cardiologists.

PMID: 30710071 [PubMed - in process]

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Cell cycle arrest in replicative senescence is not an immediate consequence of telomere dysfunction.

Cell cycle arrest in replicative senescence is not an immediate consequence of telomere dysfunction.

Mech Ageing Dev. 2019 Jan 30;:

Authors: Shamim Nassrally M, Lau A, Wise K, John N, Kotecha S, Lee KL, Brooks RF

Abstract
In replicative senescence, cells with critically-short telomeres activate a DNA-damage response leading to cell-cycle arrest, while those without telomere dysfunction would be expected to cycle normally. However, population growth declines more gradually than such a simple binary switch between cycling and non-cycling states would predict. We show here that late-passage cultures of human fibroblasts are not a simple mixture of cycling and non-cycling cells. Rather, although some cells had short cycle times comparable to those of younger cells, others continued to divide but with greatly extended cycle times, indicating a more-gradual approach to permanent arrest. Remarkably, in late passage cells, the majority showed prominent DNA-damage foci positive for 53BP1, yet many continued to divide. Evidently, the DNA-damage-response elicited by critically-short telomeres is not initially strong enough for complete cell-cycle arrest. A similar continuation of the cell cycle in the face of an active DNA-damage response was also seen in cells treated with a low dose of doxorubicin sufficient to produce multiple 53BP1 foci in all nuclei. Cell cycle checkpoint engagement in response to DNA damage is thus weaker than generally supposed, explaining why an accumulation of dysfunctional telomeres is needed before marked cell cycle elongation or permanent arrest is achieved.

PMID: 30710559 [PubMed - as supplied by publisher]

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miR-543 inhibites cervical cancer growth and metastasis by targeting TRPM7.

miR-543 inhibites cervical cancer growth and metastasis by targeting TRPM7.

Chem Biol Interact. 2019 Jan 30;:

Authors: Liu X, Gan L, Zhang J

Abstract
Dysregulation of miR-543 has been implicated to play crucial roles in various human cancers. However, the function of miR-543 involved in cervical cancer (CC) progress remains largely unknown. Thus, this study aimed to explore the potential role of miR-543 and the underlying mechanisms in human CC. In this study, we found that miR-543 was significantly downregulated in 69 CC tissue samples and cell lines when compared to adjacent normal tissues and cell line. Decreased miR-543 was closely correlated with poor clinicopathological parameters including larger tumor size, late FIGO stage and lymph node metastasis. Overexpression of miR-543 in CC cell lines remarkably inhibited cell proliferation, invasion and migration, caused cell cycle arrest, promoted apoptosis in vitro, and suppressed tumor growth in vivo, whereas miR-543 inhibitor showed the opposite effect. Dual-luciferase assay validated that 3'-untranslated region (UTR) of transient receptor potential melastatin 7 (TRPM7) was a direct binding site of miR-543. Rescue experiments showed that restoration of TRPM7 expression partially reversed the miR-543-mediated inhibition of proliferation and invasion in CC cells. Further studies confirmed that P13K/AKT and p38/MAPK signaling was involved in miR-543/TRPM7 axis mediated CC progression. Thus, these findings demonstrated the tumor suppressor role of miR-543 on CC progression, which might serve as a potential biomarker for CC diagnosis and therapy.

PMID: 30710498 [PubMed - as supplied by publisher]

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Identification of stable senescence-associated reference genes.

Identification of stable senescence-associated reference genes.

Aging Cell. 2019 Feb 01;:e12911

Authors: Hernandez-Segura A, Rubingh R, Demaria M

Abstract
Cellular senescence is a state of permanent cell cycle arrest activated in response to damaging stimuli. Many hallmarks associated with senescent cells are measured by quantitative real-time PCR (qPCR). As the selection of stable reference genes for interpretation of qPCR data is often overlooked, we performed a systematic review to understand normalization strategies entailed in experiments involving senescent cells. We found that, in violation of the Minimum Information for publication of qPCR Experiments (MIQE) guidelines, most reports used only one reference gene to normalize qPCR data, and that stability of the reference genes was either not tested or not reported. To identify new and more stable reference genes in senescent fibroblasts, we analyzed the Shapiro-Wilk normality test and the coefficient of variation per gene using in public RNAseq datasets. We then compared the new reference gene candidates with commonly used ones by using both RNAseq and qPCR data. Finally, we defined the best reference genes to be used universally or in a strain-dependent manner. This study intends to raise awareness of the instability of classical reference genes in senescent cells and to serve as a first attempt to define guidelines for the selection of more reliable normalization methods.

PMID: 30710410 [PubMed - as supplied by publisher]

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The deubiquitylase OTUB1 mediates ferroptosis via stabilization of SCL7A11.

The deubiquitylase OTUB1 mediates ferroptosis via stabilization of SCL7A11.

Cancer Res. 2019 Feb 01;:

Authors: Liu T, Jiang L, Tavana O, Gu W

Abstract
Although cell cycle arrest, senescence, and apoptosis are established mechanisms of tumor suppression, accumulating evidence reveals that ferroptosis, an iron-dependent, non-apoptotic form of cell death, represents a new regulatory pathway in suppressing tumor development. Ferroptosis is triggered by lipid peroxidation and is tightly regulated by SLC7A11, a key component of the cystine-glutamate antiporter. Although many studies demonstrate the importance of transcriptional regulation of SLC7A11 in ferroptotic responses, it remains largely unknown how the stability of SLC7A11 is controlled in human cancers. In this study, we utilized biochemial purification to identify the ubiquitin hydrolase OTUB1 as a key factor in modulating SLC7A11 stability. OTUB1 directly interacted with and stabilized SLC7A11; conversely, OTUB1 knockdown diminished SLC7A11 levels in cancer cells. OTUB1 was overexpressed in human cancers, and inactivation of OTUB1 destabilized SLC7A11 and led to growth suppression of tumor xenografts in mice, which was associated with reduced activation of ferroptosis. Notably, overexpression of the cancer stem cell marker CD44 enhanced the stability of SLC7A11 by promoting the interaction between SLC7A11 and OTUB1; depletion of CD44 partially abrogated this interaction. CD44 expression suppressed ferroptosis in cancer cells in an OTUB1-dependent manner. Together, these results show that OTUB1 plays an essential role in controlling the stability of SLC7A11 and the CD44-mediated effects on ferroptosis in human cancers.

PMID: 30709928 [PubMed - as supplied by publisher]

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Cell Cycle Arrest in Different Cancer Cell Lines (Liver, Breast, and Colon) Induces Apoptosis under the Influence of the Chemical Content of Aeluropus lagopoides Leaf Extracts.

Cell Cycle Arrest in Different Cancer Cell Lines (Liver, Breast, and Colon) Induces Apoptosis under the Influence of the Chemical Content of Aeluropus lagopoides Leaf Extracts.

Molecules. 2019 Jan 31;24(3):

Authors: Saleh KA, Albinhassan TH, Elbehairi SEI, Alshehry MA, Alfaifi MY, Al-Ghazzawi AM, Al-Kahtani MA, Alasmari ADA

Abstract
Natural products, especially secondary metabolites produced by plants under stressed conditions, are shown to have different pharmacological impacts from one to another. Aeluropus lagopoides is one of the common halophyte plants that survive under stressed conditions, and has been used for healing wounds and as a painkiller. The bioactivity and the chemical composition of this plant have been poorly investigated. Consequently, the chemical components of A. lagopoides leaves were extracted using hexane (nonpolar), ethyl acetate (semi-polar), and n-butanol (polar) to extract the most extensive variety of metabolites. The cytotoxicity and anticancer impact of extracted secondary metabolites were evaluated against breast (MCF-7), colon (HCT-116), and liver (HepG2) cancer cell lines using a SulphoRhodamine-B (SRB) test. Their mechanisms of action were verified by observing the appearance of apoptotic bodies using the fluorescent microscope, while their antiproliferative impacts were evaluated using a flow cytometer. Results revealed that secondary metabolites extracted using hexane and ethyl acetate had the highest cytotoxicity and thus the greatest anticancer activity effect on HepG2 with IC50 (24.29 ± 0.85 and 11.22 ± 0.679 µg/mL, respectively). On the other hand, flow cytometer results showed that secondary metabolites could inhibit the cell cycle in the G0/G1 phase. To ascertain the chemical composition⁻function relationship, the extracts were analyzed using LC-MS/MS. Accordingly, A. lagopoides hexane and ethyl acetate extracts may contain agents with anticancer potential.

PMID: 30708938 [PubMed - in process]

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Sleep Surgery in the Era of Precision Medicine

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s): Stanley Yung-Chuan Liu, Robert Wayne Riley, Anthony Pogrel, Christian Guilleminault

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Proteome analysis of non-small cell lung cancer cell line secretomes and patient sputum reveals biofluid biomarker candidates for cisplatin response prediction.

Proteome analysis of non-small cell lung cancer cell line secretomes and patient sputum reveals biofluid biomarker candidates for cisplatin response prediction.

J Proteomics. 2019 Jan 30;:

Authors: Böttger F, Schaaij-Visser TBM, de Reus I, Piersma SR, Pham TV, Nagel R, Brakenhoff RH, Thunnissen E, Smit EF, Jimenez CR

Abstract
Molecular markers are urgently needed to select non-small cell lung cancer (NSCLC) patients most likely to benefit from platinum-based chemotherapies. Of particular interest are proteins that can be found in biofluids like sputum for non-invasive detection. Therefore, we profiled the secretomes of 6 NSCLC cell lines with varying IC50-values for cisplatin, using label-free GeLC-MS/MS-based proteomics. Out of a total dataset of 2610 proteins, 304 proteins showed significant differences in expression levels between cisplatin sensitive and insensitive cell lines. Functional data mining revealed that the secretion of typically extracellular factors was associated with a higher sensitivity towards cisplatin, while cisplatin insensitivity correlated with increased secretion of theoretically intra-cellular proteins. Stringent statistical analysis and quantitative filtering yielded 58 biomarker candidates, 34 of which could be detected in clinical biofluids of lung cancer patients such as sputum using label-free LC-MS/MS-based proteomics. To assess performance of these biofluid biomarker candidates, we correlated protein expression with patient survival using a publically available clinical gene expression data set (GSE14814). We thus identified 3 top candidates with potential predictive value in determining cisplatin response (UGGT1, COL6A1 and MAP4) for future development as non-invasive biomarkers to guide treatment decisions. SIGNIFICANCE: Platinum-based chemotherapies are still the standard of care for NSCLC and other lung cancer types in the clinic today. However, due to chemoresistance, many patients suffer from the toxic side effects of this treatment without gaining any benefit in terms of survival. To date, no molecular biomarkers are available to predict clinical outcome of platinum-based chemotherapy. Because proteins present the functional read-out of genetic, epigenetic and translational events in the cell, a protein test is likely to be particularly suitable for response prediction. Of high relevance are proteins that are shed or secreted from cells, for example at primary tumor sites, and can be found in easily accessible biofluids like sputum for non-invasive detection. Here, we report the proteome profiling of the conditioned media (secretomes) of a panel of NSCLC cell lines in relation to cisplatin IC50 values, as a pre-clinical model, and of patient sputum as a clinical, lung cancer relevant biofluid. Using this approach in conjunction with exploration of the predictive potential in a transcriptome lung cancer patient dataset, we reveal biofluid biomarker candidates that, with further validation, may be used for non-invasive cisplatin response prediction in the future.

PMID: 30710758 [PubMed - as supplied by publisher]

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Epigenetic regulation of iASPP-p63 feedback loop in cutaneous squamous cell carcinoma.

Epigenetic regulation of iASPP-p63 feedback loop in cutaneous squamous cell carcinoma.

J Invest Dermatol. 2019 Jan 30;:

Authors: Robinson DJ, Patel A, Purdie KJ, Wang J, Rizvi H, Hufbauer M, Ostano P, Akgül B, Chiorino G, Harwood C, Bergamaschi D

Abstract
Keratinocyte skin cancer, comprising cutaneous squamous (cSCC) and basal cell carcinoma, is the most common malignancy in the UK. P53 is frequently mutated in cSCC. iASPP is a key inhibitor of p53 and NF-kB signalling pathways and has been documented as highly expressed in several types of human cancer. We have previously identified an autoregulatory feedback loop between iASPP and p63, which is critical in epidermal homeostasis. We hypothesised a potential role for dysregulation of this axis in the pathogenesis of keratinocyte malignancies. Immunostaining of 116 cSCC clinical samples revealed increased iASPP and ΔNp63 expression but also highlighted a significant alteration of iASPP cellular localisation, with consequent deregulation of its function. Expression patterns, functionality, gene and microRNA expression analysis were further investigated in 10 cSCC cell lines. Our data suggest that whilst direct effects of iASPP and p63 upon each other's expression are maintained in cSCC, epigenetic dysregulation of the feedback loop occurs at the microRNA level by a previously unreported mechanism controlling p63 expression. We demonstrate that this autoregulatory feedback loop controls cell migration in cSCC by blocking EMT and promoting proliferation and provides future directions for clinical biomarker and therapeutic target discovery in cutaneous SCC.

PMID: 30710576 [PubMed - as supplied by publisher]

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Disease-free survival as a surrogate for overall survival in patients with HER2-positive, early breast cancer in trials of adjuvant trastuzumab for up to 1 year: a systematic review and meta-analysis.

Disease-free survival as a surrogate for overall survival in patients with HER2-positive, early breast cancer in trials of adjuvant trastuzumab for up to 1 year: a systematic review and meta-analysis.

Lancet Oncol. 2019 Jan 29;:

Authors: Saad ED, Squifflet P, Burzykowski T, Quinaux E, Delaloge S, Mavroudis D, Perez E, Piccart-Gebhart M, Schneider BP, Slamon D, Wolmark N, Buyse M

Abstract
BACKGROUND: Although frequently used as a primary endpoint, disease-free survival has not been validated as a surrogate for overall survival in early breast cancer. We investigated this surrogacy in the adjuvant setting of treatment with anti-HER2 antibodies.
METHODS: In a systematic review and meta-analysis, we identified published and non-published randomised controlled trials with completed accrual and available disease-free survival and overall survival results for the intention-to-treat population as of September 2016. Bibliographic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials), clinical trial registries (Clinicaltrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, and PharmNet.Bund), and trial registries from relevant pharmaceutical companies were searched. Eligibility for treatment of HER2-positive early breast cancer required at least one group to have an anti-HER antibody treatment (ie, trastuzumab, pertuzumab, or trastuzumab emtansine) planned for 12 months, and at least one control arm with chemotherapy without the antibody, a lower total dose or duration of the antibody, or observation alone. Units of analysis were contrasts: two-group trials gave rise to one contrast, whereas trials with more than two groups gave rise to more than one contrast. We excluded trials enrolling patients with recurrent, metastatic, or non-invasive disease, and those testing neoadjuvant therapy exclusively. Our primary objective was to estimate patient-level and trial-level correlations between disease-free survival and overall survival. We measured the association between disease-free survival and overall survival using Spearman's correlation coefficient (rs), and the association between hazard ratios (HRs) for disease-free survival and overall survival using R2. We computed the surrogate threshold effect, the maximum HR for disease-free survival that statistically predicts an HR for overall survival less than 1·00 in a future trial.
FINDINGS: Eight trials (n=21 480 patients) gave rise to a full set (12 contrasts). Patient-level associations between disease-free and overall survival were strong (rs=0·90 [95% CI 0·89-0·90]). Trial-level associations gave rise to values of R2 of 0·75 (95% CI 0·50-1·00) for the full set. Subgroups defined by nodal straws and hormone receptor status yielded qualitatively similar results. Depending on the expected number of deaths in a future trial, the surrogate threshold effects ranged from 0·56 to 0·81, based on the full set.
INTERPRETATION: These findings suggest that it is appropriate to continue to use disease-free survival as a surrogate for overall survival in trials in HER-2-positive, early breast cancer. The key limitation of this study is the dependence of its results on the trials included and on the existence of an outlying trial.
FUNDING: Roche Pharma AG.

PMID: 30709633 [PubMed - as supplied by publisher]

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Tolerability and activity of ublituximab, umbralisib, and ibrutinib in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: a phase 1 dose escalation and expansion trial.

Tolerability and activity of ublituximab, umbralisib, and ibrutinib in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: a phase 1 dose escalation and expansion trial.

Lancet Haematol. 2019 Feb;6(2):e100-e109

Authors: Nastoupil LJ, Lunning MA, Vose JM, Schreeder MT, Siddiqi T, Flowers CR, Cohen JB, Burger JA, Wierda WG, O'Brien S, Sportelli P, Miskin HP, Purdom MA, Weiss MS, Fowler NH

Abstract
BACKGROUND: Therapeutic approaches for B-cell malignancies continue to evolve, especially with regard to combination approaches. We assessed the safety and efficacy of the triplet ublituximab, umbralisib, and ibrutinib in patients with advanced B-cell malignancies.
METHODS: We did an open-label, phase 1 study with dose-escalation and dose-expansion phases, at five centres in the USA. Eligible patients were aged 18 years or older with histologically confirmed lymphocytic leukaemia or relapsed or refractory B-cell non-Hodgkin lymphoma, had measurable disease, adequate organ function, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less. Patients with known CNS lymphoma, active hepatitis B or C infection, or HIV were excluded. In the dose-escalation cohort, patients were treated in cycles of 28 days with escalating doses of oral umbralisib (400, 600, or 800 mg) and fixed doses of intravenous ublituximab (900 mg) and oral ibrutinib (420 mg for patients with chronic lymphocytic leukaemia; 560 mg for patients with B-cell non-Hodgkin lymphoma) in a standard 3 × 3 design until disease progression or intolerance. In the dose-expansion phase, patients were given the recommended dose of the drug combination as determined from the dose-escalation phase. The primary endpoints were safety, dose-limiting toxicities, and the maximum tolerated dose of umbralisib, when given in combination with ublituximab and ibrutinib. Safety was assessed in patients who received at least one dose of study drug; activity was assessed in all patients who had at least one post-treatment efficacy measurement. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT02006485.
FINDINGS: Between Sept 2, 2014, and Nov 6, 2017, we enrolled 46 patients: 24 in the dose-escalation cohort (n=14 chronic lymphocytic leukaemia or small lymphocytic lymphoma; n=10 B-cell non-Hodgkin lymphoma) and 22 in the dose-expansion cohort (n=9 chronic lymphocytic leukaemia or small lymphocytic lymphoma; n=13 B-cell non-Hodgkin lymphoma). 46 patients received at least one dose of study drug. The maximum tolerated dose of umbralisib was not reached. The recommended dose for the dose-expansion phase was umbralisib 800 mg orally once daily plus ibrutinib orally once daily and intravenous ublituximab 900 mg administered on days 1, 8, and 15 of cycle 1, day 1 of cycles 2-6, and on day 1 of cycles 9 and 12. 37 (84%) of 44 patients achieved an overall response (complete or partial response). The most common any-grade adverse events were diarrhoea (n=27 [59%]), fatigue (n=23 [50%]), infusion-related reaction (n=20 [43%]), dizziness (n=17 [37%]), nausea (n=17 [37%]), and cough (n=16 [35%]). Grade 3-4 adverse events were manageable with the most common being neutropenia (n=10 [22%]) and cellulitis (n=6 [13%]). Serious adverse events occurred in 11 (24%) of 46 patients and included rash (n=2 [4%]), pneumonia (n=2 [4%]), atrial fibrillation (n=2 [4%]), sepsis (n=2 [4%]), abdominal pain (n=1 [2%]), syncope (n=1 [2%]), cellulitis (n=1 [2%]), pneumonitis (n=1 [2%]), headache (n=1 [2%]), lung infection (n=1 [2%]), skin infection (n=1 [2%]), pleural effusion (n=1 [2%]), pericardial infusion (n=1 [2%]), upper gastrointestinal bleeding (n=1 [2%]), diarrhoea (n=1 [2%]), and weakness (n=1 [2%]). No deaths related to adverse events occurred.
INTERPRETATION: The combination of ublituximab, umbralisib, and ibrutinib seems to be tolerable and is associated with encouraging activity in advanced chronic lymphocytic leukaemia and B-cell non-Hodgkin lymphoma. This triplet combination will require further investigation in future studies to improve understanding of this novel, chemotherapy-free triplet combination in the management of these cancers.
FUNDING: TG Therapeutics.

PMID: 30709431 [PubMed - in process]

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Pediatric Tongue Base Surgery

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s): Gi Soo Lee, Umakanth Katwa

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Upper Airway (Hypoglossal Nerve) Stimulation for Treatment of Obstructive Sleep Apnea

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s): Rishi Jay Gupta, Deepak Kademani, Stanley Yung-Chuan Liu

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Bilateral Temporomandibular Joint Reconstruction and Maxillomandibular Advancement for Concomitant Temporomandibular Joint Degeneration and Obstructive Sleep Apnea

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s): Rishi Jay Gupta, Rebeka Silva, Stephen T. Connelly

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Maxillomandibular Advancement: The Canadian Experience

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s): Mélinda Paris, Simon Jean, Carl Bouchard

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Maxillomandibular Advancement: Contemporary Approach at Stanford

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s): Stanley Yung-Chuan Liu, Michael Awad, Robert Wayne Riley

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Genioglossus and Genioplasty Advancement

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s): Allen Cheng

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Drug-Induced Sleep Endoscopy

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s): Michael Awad, Tyler S. Okland, Vladimir Nekhendzy

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Sleep Surgery: From Reconstruction to Restoration and Re-education

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s): Stanley Yung-Chuan Liu

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Forthcoming Issues

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s):

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Contents

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s):

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Contributors

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s):

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Copyright

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s):

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Sleep Surgery

Publication date: March 2019

Source: Atlas of the Oral and Maxillofacial Surgery Clinics, Volume 27, Issue 1

Author(s): Stanley Yung-Chuan Liu

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Neoadjuvant Management of Early Breast Cancer: A Clinical and Investigational Position Statement.

Neoadjuvant Management of Early Breast Cancer: A Clinical and Investigational Position Statement.

Oncologist. 2019 Feb 01;:

Authors: Colomer R, Saura C, Sánchez-Rovira P, Pascual T, Rubio IT, Burgués O, Marcos L, Rodríguez CA, Martín M, Lluch A

Abstract
BACKGROUND: Neoadjuvant treatment is increasingly one of the preferred therapeutic options for early breast cancer and may have some unique outcomes, such as identifying predictive and prognostic factors of response or increasing the knowledge of individual tumor biology.
DESIGN: A panel of experts from different specialties reviewed published clinical studies on the neoadjuvant management of breast cancer. Recommendations were made that emphasized the clinical multidisciplinary management and the investigational leverage in early breast cancer.
RESULTS: Neoadjuvant therapy has equivalent efficacy to adjuvant therapy, and it has some additional benefits that include increasing breast conservation, assessing tumor response, establishing prognosis based on the pathological response, and providing a "second opportunity" for nonresponding patients. Achieving pathological complete remission because of neoadjuvant therapy has been correlated with long-term clinical benefit, particularly in HER2-positive and triple-negative breast cancer. In addition, the neoadjuvant setting is a powerful model for the development of new drugs and the identification of prognostic markers. Finally, neoadjuvant therapy has proven to be cost-effective by reducing nondrug costs, avoiding radical surgery, and reducing hospital stays when compared with other treatment approaches.
CONCLUSION: Neoadjuvant therapy has clinical benefits in early breast cancer and provides in vivo information of individual breast cancer biology while allowing the investigation of new treatment approaches. Access to neoadjuvant therapy should be an option available to all patients with breast cancer through multidisciplinary tumor management.
IMPLICATIONS FOR PRACTICE: Neoadjuvant treatment should be strongly considered as a therapeutic option for localized breast cancer and is a powerful tool for understanding breast cancer biology and investigating new treatment approaches.

PMID: 30710068 [PubMed - as supplied by publisher]

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Disease-free survival as a surrogate for overall survival in patients with HER2-positive, early breast cancer in trials of adjuvant trastuzumab for up to 1 year: a systematic review and meta-analysis.

Disease-free survival as a surrogate for overall survival in patients with HER2-positive, early breast cancer in trials of adjuvant trastuzumab for up to 1 year: a systematic review and meta-analysis.

Lancet Oncol. 2019 Jan 29;:

Authors: Saad ED, Squifflet P, Burzykowski T, Quinaux E, Delaloge S, Mavroudis D, Perez E, Piccart-Gebhart M, Schneider BP, Slamon D, Wolmark N, Buyse M

Abstract
BACKGROUND: Although frequently used as a primary endpoint, disease-free survival has not been validated as a surrogate for overall survival in early breast cancer. We investigated this surrogacy in the adjuvant setting of treatment with anti-HER2 antibodies.
METHODS: In a systematic review and meta-analysis, we identified published and non-published randomised controlled trials with completed accrual and available disease-free survival and overall survival results for the intention-to-treat population as of September 2016. Bibliographic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials), clinical trial registries (Clinicaltrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, and PharmNet.Bund), and trial registries from relevant pharmaceutical companies were searched. Eligibility for treatment of HER2-positive early breast cancer required at least one group to have an anti-HER antibody treatment (ie, trastuzumab, pertuzumab, or trastuzumab emtansine) planned for 12 months, and at least one control arm with chemotherapy without the antibody, a lower total dose or duration of the antibody, or observation alone. Units of analysis were contrasts: two-group trials gave rise to one contrast, whereas trials with more than two groups gave rise to more than one contrast. We excluded trials enrolling patients with recurrent, metastatic, or non-invasive disease, and those testing neoadjuvant therapy exclusively. Our primary objective was to estimate patient-level and trial-level correlations between disease-free survival and overall survival. We measured the association between disease-free survival and overall survival using Spearman's correlation coefficient (rs), and the association between hazard ratios (HRs) for disease-free survival and overall survival using R2. We computed the surrogate threshold effect, the maximum HR for disease-free survival that statistically predicts an HR for overall survival less than 1·00 in a future trial.
FINDINGS: Eight trials (n=21 480 patients) gave rise to a full set (12 contrasts). Patient-level associations between disease-free and overall survival were strong (rs=0·90 [95% CI 0·89-0·90]). Trial-level associations gave rise to values of R2 of 0·75 (95% CI 0·50-1·00) for the full set. Subgroups defined by nodal straws and hormone receptor status yielded qualitatively similar results. Depending on the expected number of deaths in a future trial, the surrogate threshold effects ranged from 0·56 to 0·81, based on the full set.
INTERPRETATION: These findings suggest that it is appropriate to continue to use disease-free survival as a surrogate for overall survival in trials in HER-2-positive, early breast cancer. The key limitation of this study is the dependence of its results on the trials included and on the existence of an outlying trial.
FUNDING: Roche Pharma AG.

PMID: 30709633 [PubMed - as supplied by publisher]

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Endpoint selection in HER2-positive early breast cancer.

Endpoint selection in HER2-positive early breast cancer.

Lancet Oncol. 2019 Jan 29;:

Authors: Amir E

PMID: 30709632 [PubMed - as supplied by publisher]

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Prevalence of germline mutations in the TP53 gene in patients with early-onset breast cancer in the Mexican population.

Prevalence of germline mutations in the TP53 gene in patients with early-onset breast cancer in the Mexican population.

BMC Cancer. 2019 Feb 01;19(1):118

Authors: Gallardo-Alvarado LN, Tusié-Luna MT, Tussié-Luna MI, Díaz-Chávez J, Segura YX, Bargallo-Rocha E, Villarreal C, Herrera-Montalvo LA, Herrera-Medina EM, Cantu-de Leon DF

Abstract
BACKGROUND: Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients.
METHODS: We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control.
RESULTS: We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53.
CONCLUSIONS: Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.

PMID: 30709381 [PubMed - in process]

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Anatomical features of primary brain tumors affect seizure risk and semiology.

Anatomical features of primary brain tumors affect seizure risk and semiology.

Neuroimage Clin. 2019 Jan 25;22:101688

Authors: Akeret K, Serra C, Rafi O, Staartjes VE, Fierstra J, Bellut D, Maldaner N, Imbach LL, Wolpert F, Poryazova R, Regli L, Krayenbühl N

Abstract
OBJECTIVE: An epileptic seizure is the most common clinical manifestation of a primary brain tumor. Due to modern neuroimaging, detailed anatomical information on a brain tumor is available early in the diagnostic process and therefore carries considerable potential in clinical decision making. The goal of this study was to gain a better understanding of the relevance of anatomical tumor characteristics on seizure prevalence and semiology.
METHODS: We reviewed prospectively collected clinical and imaging data of all patients operated on a supratentorial intraparenchymal primary brain tumor at our department between January 2009 and December 2016. The effect of tumor histology, anatomical location and white matter infiltration on seizure prevalence and semiology were assessed using uni- and multivariate analyses.
RESULTS: Of 678 included patients, 311 (45.9%) presented with epileptic seizures. Tumor location within the central lobe was associated with higher seizure prevalence (OR 4.67, 95% CI: 1.90-13.3, p = .002), especially within the precentral gyrus or paracentral lobule (100%). Bilateral extension, location within subcortical structures and invasion of deeper white matter sectors were associated with a lower risk (OR 0.45, 95% CI: 0.25-0.78; OR 0.10, 95% CI: 0.04-0.21 and OR 0.39, 95% CI: 0.14-0.96, respectively). Multivariate analysis revealed the impact of a location within the central lobe on seizure risk to be highly significant and more relevant than histopathology (OR: 4.79, 95% CI: 1.82-14.52, p = .003). Seizures due to tumors within the central lobe differed from those of other locations by lower risk of secondary generalization (p < .001).
CONCLUSIONS: Topographical lobar and gyral location, as well as extent of white matter infiltration impact seizure risk and semiology. This finding may have a high therapeutic potential, for example regarding the use of prophylactic antiepileptic therapy.

PMID: 30710869 [PubMed - as supplied by publisher]

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Crosslink between Temozolomide and PD-L1 immune-checkpoint inhibition in glioblastoma multiforme.

Crosslink between Temozolomide and PD-L1 immune-checkpoint inhibition in glioblastoma multiforme.

BMC Cancer. 2019 Feb 01;19(1):117

Authors: Heynckes S, Daka K, Franco P, Gaebelein A, Frenking JH, Doria-Medina R, Mader I, Delev D, Schnell O, Heiland DH

Abstract
BACKGROUND: In recent years, PD-1/PD-L1 immune checkpoint inhibitors have improved cancer therapy in many tumor types, but no benefit of immune checkpoint therapy has been found in glioblastoma multiforme (GBM). Based on the results of our earlier work, which showed a reduction of PD-L1 expression in patients treated with temozolomide (TMZ), we aimed to investigate the link between TMZ therapy and the immune control point target PD-L1.
METHODS: RNA-sequencing data from de-novo and recurrent glioblastoma were analyzed by AutoPipe algorithm. Results were confirmed either in a cell model by two primary and one established GBM cell line and specimens of de-novo and recurrent GBM. PD-L1 and pathway activation of the JAK/STAT pathway was analyzed by quantitative real-time PCR and western blot.
RESULTS: We found a significant downregulation of the JAK/STAT pathway and immune response in recurrent tumors. The cell model showed an upregulation of PD-L1 after IFNγ treatment, while additional TMZ treatment lead to a reduction of PD-L1 expression and JAK/STAT pathway activation. These findings were confirmed in specimens of de-novo and recurrent glioblastoma.
CONCLUSIONS: Our results suggest that TMZ therapy leads to a down-regulation of PD-L1 in primary GBM cells. These results support the clinical findings where PD-L1 is significantly reduced in recurrent GBMs. If the target is diminished, it may also lead to impaired efficacy of PD-1/PD-L1 inhibitors such as nivolumab.

PMID: 30709339 [PubMed - in process]

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Esophageal schwannoma: Case report and epidemiological, clinical, surgical and immunopathological analysis.

Esophageal schwannoma: Case report and epidemiological, clinical, surgical and immunopathological analysis.

Int J Surg Case Rep. 2019 Jan 10;55:69-75

Authors: Souza LCA, Pinto TDA, Cavalcanti HOF, Rezende AR, Nicoletti ALA, Leão CM, Cunha VC

Abstract
INTRODUCTION: Schwannoma is a tumor of the peripheral nervous system originated in the Schwann cells of the neural sheath.
PRESENTATION OF CASE: A 43-years-old male complained of odynophagia, dysphagia and hemoptysis. The upper gastrointestinal endoscopy showed a smooth elevated lesion, 20 cm from the incisor teeth, occupying the entire lumen of the esophagus. The chest computed tomography (CT) scan showed a lesion of 7 cm and superior mediastinal, lower paraesophageal and cardiac enlarged lymph nodes. A posterolateral thoracotomy was performed with total esophagectomy without intraoperative complications. The anatomopathological analysis revealed fusocellular mesenchymal neoplasia of low malignancy potential. The immunohistochemical study showed positivity for S-100 protein and KI67 antibodies and absence of staining for CD117, CD34, ALK protein, SMA and Desmin. Thus, the morphological and immunohistochemical findings pointed to the diagnosis of esophageal Schwannoma.
DISCUSSION: Although rare and indolent, Schwannoma occurs in the peripheral nervous system, being uncommon in the esophagus.
CONCLUSION: The immunohistochemical study is essential for the diagnosis, which is based on the positivity for S-100 protein and absence of staining for CD34 and CD117.

PMID: 30710876 [PubMed - as supplied by publisher]

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Peripontomedullary hydatid cyst: Case report and literature review.

Peripontomedullary hydatid cyst: Case report and literature review.

Int J Surg Case Rep. 2019 Jan 18;55:23-27

Authors: Alkhotani A, Butt B, Khalid M, Binmahfoodh M

Abstract
INTRODUCTION: Hydatid cyst represents the parasitic infection by Genus Echenococcus Granulosis. This disease usually involves liver followed by lungs and rarely the CNS. The CNS involvement by the Hydatid Cyst is present in 1-2% of all hydatidosis. Even when it is found in the Brain it presents usually in the supratentorial compartment. However this case was unique in having the Hydatid cyst within the infratentorial fossa. With multiple small cysts, causing mass effect and challenging for surgical resection.
PRESENTATION: A 44 years female presented with headache, diplobia and bulbar symptoms, followed by ataxia. Full examination, proper investigations showed the peripontomedullary hydatid cysts. Surgical management is illustrated.
DISCUSSION: It is still challenging for the neurosurgeons to operate on these lesions in spite of modern technologies and fancy approaches due to its delicate nature, associated risk of allergic reaction, cyst's material dissemination and irreversible injury of multiple neurological structure due to prolonged compression of cranial nerves crossing the cerebellopontine angle.
CONCLUSION: In this case report we are presenting a rare case of Multiple Hydatid cysts involving a rare location in the brain; peripontomedullary area and extending all the way down to the foramen magnum. Supported with a literature review in relation to disease etiology, epidemiology, clinical presentation and management.

PMID: 30710875 [PubMed - as supplied by publisher]

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GLP-1 mediated improvement of the glucose tolerance in the T2DM GK rat model after massive jejunal resection

Publication date: Available online 2 February 2019

Source: Annals of Anatomy - Anatomischer Anzeiger

Author(s): J. Arturo Prada-Oliveira, Alonso Camacho-Ramírez, Jesús Salas-Alvarez, Francisco Javier Campos-Martínez, Alfonso M. Lechuga-Sancho, David Almorza-Gomar, Manuel Blandino-Rosano, Gonzalo M. Pérez-Arana

Abstract

Objective

The aim of this study was to clarify the role of the middle gut in the entero-pancreatic axis modification that leads to glucose improvement in the Goto-Kakizaki (GK) rat as a non-obese T2DM model.

Background

Bariatric surgery is considered an assured solution for type 2 Diabetes (T2DM). Enterohormones such as ghrelin, gastric inhibitory polypeptide and mainly glucagon-like peptide-1 (GLP-1) were recognized as key players in the physiophathological mechanisms associated with entero-pancreatic axis regulation and glucose tolerance improvement. However, the influence of anatomical arrangements post-bariatric surgery on this axis is still debatable.

Method

To this purpose, 50% of small intestine resections were performed on GK rats (n = 6), preserving the proximal half of the jejunum and the ileum (IR50). Phenotypic and functional changes, such as performance in oral glucose tolerance tests, ileal release of GLP-1, beta-cell sensitivity to GLP-1, beta-cell mass, and turnover were characterized in IR50 and the surgical control group (Sham).

Results

The glucose tolerance was improved and ileal release of GLP-1 was enhanced four weeks after IR50 versus the control group rats. Beta-cell mass, beta-cell proliferation, and beta-cell sensitivity to GLP-1 were also increased in the pancreas of IR50 versus the control group rats.

Conclusion

the jejunal exclusion increases beta-cell-mass and improves glucose tolerance by increasing in GLP-1 expression and number of receptors via the entero-pancreatic axis.

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Severe asthma in children: therapeutic considerations

Purpose of review Children with poor asthma control despite maximal maintenance therapy have problematic severe asthma (PSA). A step-wise approach including objective adherence monitoring and a detailed multidisciplinary team assessment to identify modifiable factors contributing to poor control is needed prior to considering therapy escalation. Pathophysiological phenotyping in those with true severe therapy-resistant asthma (STRA) and the current array of add-on therapies will be discussed. Recent findings Adherence monitoring using electronic devices has shown that only 20–30% of children with PSA have STRA and need additional therapies. Omalizumab and mepolizumab are licensed for children with STRA aged 6 years and older. Although robust safety and efficacy data, with reduced exacerbations, are available for omalizumab, biomarkers predicting response to treatment are lacking. Paediatric safety data are available for mepolizumab, but efficacy data are unknown for those aged 6–11 years and minimal for those 12 years and older. A sub-group of children with STRA have neutrophilia, but the clinical significance and contribution to disease severity remains uncertain. Summary Most children with PSA have steroid sensitive disease which improves with adherence to maintenance inhaled corticosteroids. Add-on therapies are only needed for the minority with STRA. Paediatric efficacy data of novel biologics and biomarkers that identify the optimal add-on for each child are lacking. If we are to progress toward individualized therapy for STRA, pragmatic clinical trials of biologics in accurately phenotyped children are needed. Correspondence to Sejal Saglani, MD, Imperial College London, London, UK. E-mail: s.saglani@imperial.ac.uk Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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